The major objectives of the proposed research are to identify and quantify the human plasma enzyme, lecithin:cholesterol acyltransferase (LCAT), in normal subjects and those with lipid metabolism abnormalities and to quantify the lipid transport proteins (apolipoproteins) in familial LCAT deficiency in order to determine the role of LCAT in lipid metabolism. First, the LCAT enzyme will be isolated and characterized. Second, a sensitive and specific radioimmunoassay will be developed to measure the enzyme. Third, the level of the enzyme will be assessed in patients with LCAT deficiency. Fourth, the patients with a deficiency of the enzyme will have their lipoproteins (fat transport proteins) isolated and characterized under steady state (fasting) conditions and in response to dietary pertubations and in vitro changes induced by the purified enzyme. Fifth, steady state levels of the LCAT enzyme will be measured in normal subjects and in those with abnormalities of lipid metabolism. Sixth, the physiological dynamics of the LCAT enzyme will be assessed in normal and hyperlipidemic subjects in response to dietary and pharmacological perturbation. BIBLIOGRAPHIC REFERENCES: Albers, J.J., Cabana, V.G., and Stahl, Y.D.B.: Purification and characterization of human plasma lecithin:cholesterol acyltransferase. Biochemistry 15:1084-1087, 1976. Albers, J.J., Wahl, P.W., Cabana, V.G., Hazzard, W.R. and Hoover, J.J.: Quantitation of apolipoprotein A-I of human plasma high density lipoprotein. Metabolism 25:633-644, 1976.